Ligand-Blocking and Agonist Antibodies Targeting TNFR2 Use Distinct Modes of Action to Induce Antitumor Immunity.

Ligand-blocking and agonist α-TNFR2 antibodies induce tumor rejection through distinct immune mechanisms in mouse models.

• Why it matters: Understanding whether to use blocking or agonist antibodies and how FcγR interactions influence efficacy is crucial for developing effective TNFR2-targeted cancer therapies.
• What they did: Researchers engineered two types of α-TNFR2 antibodies—ligand-blocking FcγR-engaging and non-ligand-blocking agonists—and tested their anti-tumor effects across multiple mouse tumor models, including combination with α-PD-1.
• The result: Both antibody types showed potent anti-tumor activity, with the ligand-blocking antibody depleting intratumoral Tregs and reprogramming myeloid cells, while the agonist directly co-stimulated T and NK cells; both ultimately activated tumor-specific CD8+ T cells.